A. SPECIFIC AIMS 1. To study the comparative influences of dietary calorie (energy restriction) selective fat restriction and selective carbohydrate restriction on cellular immunologic abnormalities that develop in autoimmune-prone mice and with aging in long-lived autoimmune-resistant mice. 2. To investigate the influence of dietary calorie (energy) restriction, selective dietary fat restriction, and selective carbohydrate restriction on development of B lineage precursor cells in autoimmune-prone NZB and long-lived autoimmune-resistant mice. 3. To determine the influences of dietary calorie (energy) restriction, selective dietary fat restriction, and selective carbohydrate restriction on decline of B lineage precursor cells in autoimmune-prone NZB and long-lived autoimmune-resistant mice. 4. To study the influence of dietary calorie (energy) restriction, selective fat restriction or selective carbohydrate restriction on endocrine metabolism and rate of DNA synthesis in the pyloric pits, bone marrow, spleen and thymus of mice from each of the several autoimmune-prone strains. 5. a. To determine whether autoimmune processes are involved in development of occlusive coronary vascular disease in autoimmune-prone mice. b. To determine whether total dietary calorie (energy), high fat or high carbohydrate intake are involved in development of coronary vascular lesions in autoimmunity-prone mice. 6. To determine whether autoimmunity-resistant, long-lived mice given a diet which will make possible development of coronary vascular lesions and atherosclerosis that occurs in short-lived, autoimmune-prone mice fed a high calorie, high saturated fat diet. For most of the experiments the mice will be individually caged, fed daily, the diets weighed, orts weighed and food intake recorded on each diet. The mice are weighed weekly and representative mice are sacrificed at 3-4 mo intervals for immunological study of lymph node and spleen cells, circulating immune complexes and serum. Studies of auto-antibodies in estrus cycles and of the influence of diets on hormone levels will be sampled at regular intervals with immuno-histochemical studies of kidney, heart, blood vessels, liver and spleen and histological study and chemical and histological analysis of heart, coronary vessels, aorta and aortic vessels will be made.